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The MMRF Immune Atlas Project

Multiple myeloma is a cancer of the immune system. In myeloma, the type of cell that becomes cancerous (i.e. grows out of control) is the plasma cell, which is a type of immune cell that normally creates molecules called antibodies that help protect the body from infection. Your immune system can recognize substances as “foreign” and create antibodies that help your immune system to eliminate them. Similarly, cancer cells can also sometimes be recognized as foreign and killed by your own body’s immune system. But all too often, cancer cells are tricky and evade detection by the immune system.

Myeloma cells grow inside the bone marrow, which is a complex cellular environment. There are many different types of cells in the bone marrow, as it is the body’s blood cell factory. How the myeloma cells interact with this environment (also known as the bone marrow microenvironment) can impact how well the myeloma cells grow and how well the body can fight them.

Back in 2019, the MMRF envisioned a collaborative project called Immune Atlas to further define the immune microenvironment in the bone marrow and the role it might play in myeloma and in how different patients respond to therapy. At the time, there was limited knowledge regarding the bone marrow environment in MM patients and how it might influence disease development, progression, and response to therapy. There had been several smaller studies, but none with the necessary number of patients to account for the differences between myeloma patients and their cancers, and the data had not been widely shared. The initial idea was to combine the genomic (DNA) and clinical treatment landscape of each patient with their immune landscape, in the hope of better understanding which patients would respond best to certain therapies.

Our first action was to create a network of 5 leading academic medical centers (Emory University, Beth Israel Deaconess, Washington University in St. Louis, Icahn School of Medicine at Mount Sinai, and Mayo Clinic) that had robust myeloma research programs. In collaboration, these 5 institutions and MMRF developed a uniform assay strategy using a common sample set to ensure that the data generated by the selected cutting-edge technology platforms (able to extract highly detailed information from patient samples at the level of a single cell) were harmonized across these centers.

Through 2020-2023, this Immune Atlas team has completed immune profiling of hundreds of bone marrow and blood samples from our CoMMpass study utilizing single cell RNA sequencing (scRNAseq) and Cytometry by Time-Of-Flight (CyTOF) assays. Analysis of both baseline (at diagnosis) and longitudinal (e.g., after stem cell transplant or at clinical response or relapse) samples allow for scientists to ask questions about the relationship between different immune cell populations and (i) patient genomics and disease risk, (ii) patients who experienced rapid progression after transplant (functional high-risk patients) and those whose remission lasted longer (standard risk patients), and (iii) changes in the immune environment over time and after treatment with doublet or triplet therapy. To date, the Immune Atlas team has generated data from over 1,100 samples collected from approximately 700 myeloma patients who were enrolled in the MMRF CoMMpass study, and has just completed and submitted a manuscript for publication in a major scientific journal describing their detailed analysis of over 1.1 million cells from 263 newly diagnosed myeloma patients.